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Information on EC 2.3.1.225 - protein S-acyltransferase and Organism(s) Homo sapiens and UniProt Accession Q9NPG8
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2.3.1.225 protein S-acyltransferaseIUBMB Comments
The enzyme catalyses the posttranslational protein palmitoylation that plays a role in protein-membrane interactions, protein trafficking, and enzyme activity. Palmitoylation increases the hydrophobicity of proteins or protein domains and contributes to their membrane association.
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Word Map
- 2.3.1.225
-
palmitoylation
- palmitate
-
s-acylation
- huntingtin
-
palmitoylation-dependent
-
huntingtin-interacting
- 2-bromopalmitate
-
s-acyltransferases
- medicine
-
autoacylation
-
16-carbon
- snap25
-
acyl-acyl
-
palmitoylation-deficient
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
hip14, dhhc3, palmitoyl acyltransferase, dhhc5, zdhhc5, dhhc2, akr1p, zdhhc3, protein acyltransferase, dhhc protein, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
DHHC2
Pat
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
palmitoyl-CoA + [protein]-L-cysteine = [protein]-S-palmitoyl-L-cysteine + CoA
two-step transfer mechanism, ping-pong kinetic mechanism
-
SYSTEMATIC NAME
IUBMB Comments
palmitoyl-CoA:[protein]-L-cysteine S-palmitoyltransferase
The enzyme catalyses the posttranslational protein palmitoylation that plays a role in protein-membrane interactions, protein trafficking, and enzyme activity. Palmitoylation increases the hydrophobicity of proteins or protein domains and contributes to their membrane association.
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
palmitoyl-CoA + [protein]-L-cysteine
[protein]-S-palmitoyl-L-cysteine + CoA
-
-
-
r
palmitoyl-CoA + [endothelial nitric oxide synthase]-L-cysteine
[endothelial nitric oxide synthase]-S-palmitoyl-L-cysteine + CoA
-
isozyme DHHC-21
-
-
r
palmitoyl-CoA + [Ga protein]-L-cysteine
[Ga protein]-S-palmitoyl-L-cysteine + CoA
substrate of DHHC3 and DHHC7
-
-
r
palmitoyl-CoA + [GAD65]-L-cysteine
[GAD65]-S-palmitoyl-L-cysteine + CoA
-
-
-
r
palmitoyl-CoA + [GAP-43 protein]-L-cysteine
[GAP-43 protein]-S-palmitoyl-L-cysteine + CoA
substrate of DHHC7 and DHHC15
-
-
r
palmitoyl-CoA + [htt(1-548)]-L-cysteine
[htt(1-548)]-S-palmitoyl-L-cysteine + CoA
N-terminal fragment of htt(1-548)
-
-
r
palmitoyl-CoA + [Lck]-L-cysteine
[Lck]-S-palmitoyl-L-cysteine + CoA
nonreceptor tyrosine kinase
-
-
r
palmitoyl-CoA + [N-myristoylated G-protein alphai1]-L-cysteine
[N-myristoylated G-protein alphai1]-S-palmitoyl-L-cysteine + CoA
-
-
-
-
r
palmitoyl-CoA + [N-myristoylated Gly-Cys-Gly tripeptide]-L-cysteine
[N-myristoylated Gly-Cys-Gly tripeptide]-S-palmitoyl-L-cysteine + CoA
-
peptide substrate si tagged via ethylenediamine with fluorescent NBD
-
-
r
palmitoyl-CoA + [PSD-95]-L-cysteine
[PSD-95]-S-palmitoyl-L-cysteine + CoA
low activity
-
-
r
palmitoyl-CoA + [Ras]-L-cysteine
[Ras]-S-palmitoyl-L-cysteine + CoA
by Ras PAT containing the DHHC9 protein subunit
-
-
r
palmitoyl-CoA + [synaptotagmin I ]-L-cysteine
[synaptotagmin I ]-S-palmitoyl-L-cysteine + CoA
-
-
-
r
palmitoyl-CoA + [protein]-L-cysteine
[protein]-S-palmitoyl-L-cysteine + CoA
-
-
-
-
r
palmitoyl-CoA + [protein]-L-cysteine
[protein]-S-palmitoyl-L-cysteine + CoA
-
-
-
r
palmitoyl-CoA + [protein]-L-cysteine
[protein]-S-palmitoyl-L-cysteine + CoA
-
-
-
r
palmitoyl-CoA + [protein]-L-cysteine
[protein]-S-palmitoyl-L-cysteine + CoA
-
S-palmitoylation is the reversible addition of palmitate or other long chain fatty acids to proteins at cysteine residues via a thioester linkage. The types of proteins that undergo palmitoylation are quite diverse and include intrinsic and peripherally associated membrane proteins, as well as mitochondrial proteins
-
-
r
palmitoyl-CoA + [PSD95]-L-cysteine
[Ras]-S-palmitoyl-L-cysteine + CoA
-
-
-
r
palmitoyl-CoA + [PSD95]-L-cysteine
[Ras]-S-palmitoyl-L-cysteine + CoA
possible substrate of DHHC15 and, to a lesser extent, DHHC2, DHHC3, and DHHC7
-
-
r
palmitoyl-CoA + [SNAP-25]-L-cysteine
[SNAP-25]-S-palmitoyl-L-cysteine + CoA
-
-
-
r
palmitoyl-CoA + [SNAP-25]-L-cysteine
[SNAP-25]-S-palmitoyl-L-cysteine + CoA
substrate of DHHC3 and DHHC7
-
-
r
additional information
?
-
-
in the absence of cellular factors, palmitoyl-CoA is capable of spontaneously S-acylating cysteinyl thiols, overview. G protein alpha subunit GsR is first acylated at Cys-3, then the palmitate is transferred to the amino group of Gly-2 through a cyclic intermediate as is postulated for hedgehog
-
-
?
additional information
?
-
-
complexity of HIP14's substrate specificity, in vitro, HIP14 has PAT activity for the N-terminal fragment of htt(1-548), SNAP-25, PSD-95, GAD65, and synaptotagmin I but not for synaptotagmin VII and paralemmin
-
-
?
additional information
?
-
complexity of HIP14's substrate specificity, in vitro, HIP14 has PAT activity for the N-terminal fragment of htt(1-548), SNAP-25, PSD-95, GAD65, and synaptotagmin I but not for synaptotagmin VII and paralemmin
-
-
?
additional information
?
-
complexity of HIP14's substrate specificity, in vitro, HIP14 has PAT activity for the N-terminal fragment of htt(1-548), SNAP-25, PSD-95, GAD65, and synaptotagmin I but not for synaptotagmin VII and paralemmin
-
-
?
additional information
?
-
-
DHHC2 has a broad protein substrate specificity. DHHC2 transfers fatty acids from all acyl-CoA chain lengths tested, consistent with it having a broad specificity for long chain acyl-CoAs, and acyl-CoAs of 14 carbons and longer inhibit palmitoyl-CoA labeling of both substrate and enzyme. The acyl-CoA chain length specificity of DHHC enzyme autoacylation parallels substrate specificity, overview
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
palmitoyl-CoA + [protein]-L-cysteine
[protein]-S-palmitoyl-L-cysteine + CoA
-
-
-
r
palmitoyl-CoA + [endothelial nitric oxide synthase]-L-cysteine
[endothelial nitric oxide synthase]-S-palmitoyl-L-cysteine + CoA
-
isozyme DHHC-21
-
-
r
palmitoyl-CoA + [Ga protein]-L-cysteine
[Ga protein]-S-palmitoyl-L-cysteine + CoA
substrate of DHHC3 and DHHC7
-
-
r
palmitoyl-CoA + [GAP-43 protein]-L-cysteine
[GAP-43 protein]-S-palmitoyl-L-cysteine + CoA
substrate of DHHC7 and DHHC15
-
-
r
palmitoyl-CoA + [Lck]-L-cysteine
[Lck]-S-palmitoyl-L-cysteine + CoA
nonreceptor tyrosine kinase
-
-
r
palmitoyl-CoA + [PSD95]-L-cysteine
[Ras]-S-palmitoyl-L-cysteine + CoA
possible substrate of DHHC15 and, to a lesser extent, DHHC2, DHHC3, and DHHC7
-
-
r
palmitoyl-CoA + [Ras]-L-cysteine
[Ras]-S-palmitoyl-L-cysteine + CoA
by Ras PAT containing the DHHC9 protein subunit
-
-
r
palmitoyl-CoA + [SNAP-25]-L-cysteine
[SNAP-25]-S-palmitoyl-L-cysteine + CoA
substrate of DHHC3 and DHHC7
-
-
r
additional information
?
-
-
in the absence of cellular factors, palmitoyl-CoA is capable of spontaneously S-acylating cysteinyl thiols, overview. G protein alpha subunit GsR is first acylated at Cys-3, then the palmitate is transferred to the amino group of Gly-2 through a cyclic intermediate as is postulated for hedgehog
-
-
?
palmitoyl-CoA + [protein]-L-cysteine
[protein]-S-palmitoyl-L-cysteine + CoA
-
-
-
-
r
palmitoyl-CoA + [protein]-L-cysteine
[protein]-S-palmitoyl-L-cysteine + CoA
-
-
-
r
palmitoyl-CoA + [protein]-L-cysteine
[protein]-S-palmitoyl-L-cysteine + CoA
-
-
-
r
palmitoyl-CoA + [protein]-L-cysteine
[protein]-S-palmitoyl-L-cysteine + CoA
-
S-palmitoylation is the reversible addition of palmitate or other long chain fatty acids to proteins at cysteine residues via a thioester linkage. The types of proteins that undergo palmitoylation are quite diverse and include intrinsic and peripherally associated membrane proteins, as well as mitochondrial proteins
-
-
r
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
-
acyl-CoAs of 14 carbons and longer inhibit palmitoyl-CoA labeling of both substrate and enzyme
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00084
[N-myristoylated Gly-Cys-Gly tripeptide]-L-cysteine
-
pH 7.4, 25°C, recombinant DHHC3
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
additional information
additional information
-
the Ras PAT activity of DHHC9/GCP16 appears to be restricted to a subset of tissues
additional information
the Ras PAT activity of DHHC9/GCP16 appears to be restricted to a subset of tissues
additional information
the Ras PAT activity of DHHC9/GCP16 appears to be restricted to a subset of tissues
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
HIP14 resides on the Golgi and can be observed on cytoplasmic vesicles
additional information
DHHC2 is present in at least some areas of the endoplasmic reticulum and Golgi
DHHC2 is present in at least some areas of the endoplasmic reticulum and Golgi
HIP14 resides on the Golgi and can be observed on cytoplasmic vesicles
additional information
the DHHC protein is not associated with early endosomes
-
additional information
the DHHC protein is not associated with early endosomes
-
additional information
the DHHC protein is not associated with early endosomes
-
additional information
the DHHC protein is not associated with early endosomes
-
additional information
the DHHC protein is not associated with early endosomes
-
additional information
the DHHC protein is not associated with early endosomes
-
additional information
-
the isozymes colocalize with eNOS in the Golgi and plasma membrane and interact with eNOS in endothelial cells
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
malfunction
physiological function
additional information
evolution
-
the enzyme is an Asp-His-His-Cys motif (DHHC) palmitoyl transferase family member
malfunction
expression of DHHC15 mutant C159S reduced PSD-95 synaptic clustering as well as the clustering of cell-surface AMPA receptor GluR2 subunits, which is dependent upon PSD-95 palmitoylation
malfunction
-
palmitoylation of wild-type eNOS by DHHC-21 is diminished by mutation of the two sites of eNOS palmitoylation, cysteines 15 and 26, palmitoylation deficient mutants of eNOS, i.e. G2A, C15/26S, and L2S, release less nitric oxide. Inhibition of DHHC-21 palmitoyl transferase, but not DHHC-3, in human endothelial cells reduces eNOS palmitoylation, eNOS targeting, and stimulated NO production
physiological function
protein palmitoylation refers to the posttranslational addition of a 16 carbon fatty acid to the side chain of cysteine, forming a thioester linkage. This acyl modification is readily reversible, providing a potential regulatory mechanism to mediate protein-membrane interactions and subcellular trafficking of proteins. Palmitoylation plays a vital role in the nervous system, where substrates are abundant
physiological function
protein palmitoylation refers to the posttranslational addition of a 16 carbon fatty acid to the side chain of cysteine, forming a thioester linkage. This acyl modification is readily reversible, providing a potential regulatory mechanism to mediate protein-membrane interactions and subcellular trafficking of proteins. Palmitoylation plays a vital role in the nervous system, where substrates are abundant. DHHC15 is a regulator of PSD-95 palmitoylation in vivo
physiological function
protein palmitoylation refers to the posttranslational addition of a 16 carbon fatty acid to the side chain of cysteine, forming a thioester linkage. This acyl modification is readily reversible, providing a potential regulatory mechanism to mediate protein-membrane interactions and subcellular trafficking of proteins. Palmitoylation plays a vital role in the nervous system, where substrates are abundant. HIP14 complements the temperature-sensitive growth phenotype and rescues the defect in receptor endocytosis that results from deleting yeast AKR1. role for HIP14 as a regulator of neuronal protein trafficking mediated by its PAT activity. HIP14's oncogenic properties are mediated through Ras proteins
physiological function
-
regulatory role of DHHC-21 in governing eNOS localization and function. eNOS fatty acylation is required for an efficient interaction with DHHC proteins and NO release, overview
physiological function
-
reversible protein palmitoylation plays a role in protein-membrane interactions, protein trafficking, and enzyme activity. Mechanisms that underlie addition and removal of palmitate from proteins, detailed overview. Palmitoylation increases the hydrophobicity of proteins or protein domains and contributes to their membrane association
physiological function
CIL56 is a synthetic oxime that can trigger a form of nonapoptotic cell death that is distinct from apoptosis, necroptosis, ferroptosis, and classic necrosis. This unconventional form of cell death is promoted by a plasma membrane protein acyltransferase complex comprising ZDHHC5 and GOLGA7
additional information
overexpression of DHHC4 does not cause increased S-acylation of LckN10-GFP
additional information
overexpression of DHHC4 does not cause increased S-acylation of LckN10-GFP
additional information
overexpression of DHHC4 does not cause increased S-acylation of LckN10-GFP
additional information
-
DHHC9 is a subunit of a human Ras PAT, but has no S-palmitoylation activity on its own, expression of human DHHC9 in yeast fails to complement an erf2DELTA strain
additional information
DHHC9 is a subunit of a human Ras PAT, but has no S-palmitoylation activity on its own, expression of human DHHC9 in yeast fails to complement an erf2DELTA strain
additional information
DHHC9 is a subunit of a human Ras PAT, but has no S-palmitoylation activity on its own, expression of human DHHC9 in yeast fails to complement an erf2DELTA strain
additional information
-
one enzyme family is lysosomal and is involved in protein degradation. The second is cytosolic and removes palmitoyl moieties preferentially from proteins associated with membranes. PAT activity requires detergent, e.g. Triton X-100, for solubilization
additional information
overexpression of DHHC2 causes increased S-acylation of LckN10-GFP. In resting Jurkat T cells, endogenous DHHC2 and Lck, a non-receptor tyrosine kinase of the Src family, are in close proximity to each other at the cell periphery, but completely non-overlapping, DHHC2 is a PAT for Lck in vivo
additional information
overexpression of DHHC2 causes increased S-acylation of LckN10-GFP. In resting Jurkat T cells, endogenous DHHC2 and Lck, a non-receptor tyrosine kinase of the Src family, are in close proximity to each other at the cell periphery, but completely non-overlapping, DHHC2 is a PAT for Lck in vivo
additional information
overexpression of DHHC2 causes increased S-acylation of LckN10-GFP. In resting Jurkat T cells, endogenous DHHC2 and Lck, a non-receptor tyrosine kinase of the Src family, are in close proximity to each other at the cell periphery, but completely non-overlapping, DHHC2 is a PAT for Lck in vivo
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). ZDHC4_HUMAN
344
5
39787
Swiss-Prot
Secretory Pathway (Reliability: 1)
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C159S
the DHHC15 mutant shows reduced activity compared to the wild-type
additional information
additional information
DHHC4 targeting with siRNA leads to Lck partial delocalization from the membranes and moving to the cytosol
additional information
DHHC4 targeting with siRNA leads to Lck partial delocalization from the membranes and moving to the cytosol
additional information
DHHC4 targeting with siRNA leads to Lck partial delocalization from the membranes and moving to the cytosol
additional information
DHHC2 targeting with siRNA leads to Lck partial delocalization from the membranes and moving to the cytosol
additional information
DHHC2 targeting with siRNA leads to Lck partial delocalization from the membranes and moving to the cytosol
additional information
DHHC2 targeting with siRNA leads to Lck partial delocalization from the membranes and moving to the cytosol
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant FLAG- and His6-tagged DHHC2 from Sf9 cells by nickel and FLAG affinity chromatography to near homogeneity
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
DHHC4, cloning of cDNA from Jurkat cells, insertion into pmCFP via pENTR/D-TOPO, and expression in T cells deficient in Lck, the T lymphocyte-specific Src family kinase, transient expression of cyan fluorescent protein CFP-tagged DHHC4 in HEK293A cells, quantitative expression analysis
DHHC16, cloning of cDNA from Jurkat cells, insertion into pmCFP via pENTR/D-TOPO, and expression in T cells deficient in Lck, the T lymphocyte-specific Src family kinase, transient expression of cyan fluorescent protein CFP-tagged DHHC16 in HEK293Acells
DHHC2, cloning of cDNA from Jurkat cells, insertion into pmCFP via pENTR/D-TOPO, and expression in T cells deficient in Lck, the T lymphocyte-specific Src family kinase, transient expression of cyan fluorescent protein CFP-tagged DHHC2 in HEK293Acells
expression of FLAG- and His6-tagged DHHC2 in Spodoptera frugiperda Sf9 cells using the baculovirus transfection system
-
expression of human DHHC9 in Saccharomyces cerevisiae fails to complement an erf2DELTA strain
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
DHHC3 is upregulated in malignant and metastatic human breast cancer. Elevated expression of DHHC3 correlates with diminished patient survival in breast cancer and six other human cancer types. DHHC3 ablation in human MDA-MB-231 mammary tumor cell xenografts reduces the sizes of both the primary tumor and metastatic lung colonies. Increased oxidative stress and senescence is observed in DHHC3-ablated cells. DHHC3-ablated tumors also show enhanced recruitment of innate immune cells associated with clearance of senescent tumors. Concomitant ablation of the upregulated oxidative stress protein TXNIP substantially negates the effects of DHHC3 depletion on oxidative stress and senescence
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Linder, M. E.; Deschenes, R. J.
New insights into the mechanisms of protein palmitoylation
Biochemistry
42
4311-4320
2003
Saccharomyces cerevisiae, Drosophila melanogaster, Homo sapiens, Rattus norvegicus
Jennings, B. C.; Linder, M. E.
DHHC protein S-acyltransferases use similar ping-pong kinetic mechanisms but display different acyl-CoA specificities
J. Biol. Chem.
287
7236-7245
2012
Homo sapiens, Mus musculus (Q8R173)
Fernandez-Hernando, C.; Fukata, M.; Bernatchez, P. N.; Fukata, Y.; Lin, M. I.; Bredt, D. S.; Sessa, W. C.
Identification of Golgi-localized acyl transferases that palmitoylate and regulate endothelial nitric oxide synthase
J. Cell. Biol.
174
369-377
2006
Homo sapiens
Mitchell, D. A.; Vasudevan, A.; Linder, M. E.; Deschenes, R. J.
Protein palmitoylation by a family of DHHC protein S-acyltransferases
J. Lipid Res.
47
1118-1127
2006
Drosophila melanogaster, Homo sapiens, Homo sapiens (Q8IUH5), Homo sapiens (Q9Y397), Saccharomyces cerevisiae
Zeidman, R.; Buckland, G.; Cebecauer, M.; Eissmann, P.; Davis, D.M.; Magee, A.I.
DHHC2 is a protein S-acyltransferase for Lck
Mol. Membr. Biol.
28
473-486
2011
Homo sapiens (Q969W1), Homo sapiens (Q9NPG8), Homo sapiens (Q9UIJ5)
Sharma, C.; Wang, H.X.; Li, Q.; Knoblich, K.; Reisenbichler, E.S.; Richardson, A.L.; Hemler, M.E.
Protein acyltransferase DHHC3 regulates breast tumor growth, oxidative stress, and senescence
Cancer Res.
77
6880-6890
2017
Homo sapiens (Q9NYG2), Homo sapiens
EXTERNAL LINKS (specific for EC-Number 2.3.1.225)
Transporter Classification Database (TCDB): 8.A.114.1.5, 8.A.114.1.3, 8.A.114.1.7, 8.A.114.1.1, 8.A.114.1.2, 8.A.114.1.6, 8.A.114.1.4
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